Publications by authors named "Lari M Koponen"

13 Publications

  • Page 1 of 1

Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation.

Brain Stimul 2021 Nov 21;15(1):116-124. Epub 2021 Nov 21.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer.

Objective: To develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region.

Methods: We designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand.

Results: The transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum.

Conclusion: The developed mTMS system enables electronically targeted brain stimulation within a cortical region.
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http://dx.doi.org/10.1016/j.brs.2021.11.014DOI Listing
November 2021

Double-Containment Coil With Enhanced Winding Mounting for Transcranial Magnetic Stimulation With Reduced Acoustic Noise.

IEEE Trans Biomed Eng 2021 07 17;68(7):2233-2240. Epub 2021 Jun 17.

Objective: This work aims to reduce the acoustic noise level of transcranial magnetic stimulation (TMS) coils. TMS requires high currents (several thousand amperes) to be pulsed through the coil, which generates a loud acoustic impulse whose peak sound pressure level (SPL) can exceed 130 dB(Z). This sound poses a risk to hearing and elicits unwanted neural activation of auditory brain circuits.

Methods: We propose a new double-containment coil with enhanced winding mounting (DCC), which utilizes acoustic impedance mismatch to contain and dissipate the impulsive sound within an air-tight outer casing. The coil winding is potted into a rigid block, which is mounted to the outer casing through the block´s acoustic nodes that are subject to minimum vibration during the pulse. The rest of the winding block is isolated from the casing by an air gap, and the sound is absorbed by polyester fiber panels within the casing. The casing thickness under the winding center is minimized to maximize the electric field output.

Results: Compared to commercial figure-of-eight TMS coils, the DCC prototype has 18-41 dB(Z) lower peak SPL at matched stimulation strength, whilst providing 28% higher maximum stimulation strength than equally focal coils.

Conclusion: The DCC design greatly reduces the acoustic noise of TMS while increasing the achievable stimulation strength.

Significance: The acoustic noise reduction from our coil design is comparable to that provided by typical hearing protection devices. This coil design approach can enhance hearing safety and reduce auditory co-activations in the brain and other detrimental effects of TMS sound.
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http://dx.doi.org/10.1109/TBME.2020.3048321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217120PMC
July 2021

Individual head models for estimating the TMS-induced electric field in rat brain.

Sci Rep 2020 10 15;10(1):17397. Epub 2020 Oct 15.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.

In transcranial magnetic stimulation (TMS), the initial cortical activation due to stimulation is determined by the state of the brain and the magnitude, waveform, and direction of the induced electric field (E-field) in the cortex. The E-field distribution depends on the conductivity geometry of the head. The effects of deviations from a spherically symmetric conductivity profile have been studied in detail in humans. In small mammals, such as rats, these effects are more pronounced due to their less spherical head, proportionally much thicker neck region, and overall much smaller size compared to the TMS coils. In this study, we describe a simple method for building individual realistically shaped head models for rats from high-resolution X-ray tomography images. We computed the TMS-induced E-field with the boundary element method and assessed the effect of head-model simplifications on the estimated E-field. The deviations from spherical symmetry have large, non-trivial effects on the E-field distribution: for some coil orientations, the strongest stimulation is in the brainstem even when the coil is over the motor cortex. With modelling prior to an experiment, such problematic coil orientations can be avoided for more accurate targeting.
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http://dx.doi.org/10.1038/s41598-020-74431-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567095PMC
October 2020

Sound comparison of seven TMS coils at matched stimulation strength.

Brain Stimul 2020 May - Jun;13(3):873-880. Epub 2020 Mar 12.

Department of Psychiatry & Behavioral Sciences, Duke University, Durham, NC, 27710, USA; Department of Electrical & Computer Engineering, Duke University, Durham, NC, 27708, USA; Department of Neurosurgery, Duke University, Durham, NC, 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA. Electronic address:

Background: Accurate data on the sound emitted by transcranial magnetic stimulation (TMS) coils is lacking.

Methods: We recorded the sound waveforms of seven coils with high bandwidth. We estimated the neural stimulation strength by measuring the induced electric field and applying a strength-duration model to account for different waveforms.

Results: Across coils, at maximum stimulator output and 25 cm distance, the sound pressure level (SPL) was 98-125 dB(Z) per pulse and 76-98 dB(A) for a 20 Hz pulse train. At 5 cm distance, these values were estimated to increase to 112-139 dB(Z) and 90-112 dB(A), respectively.

Conclusions: The coils' airborne sound can exceed some exposure limits for TMS subjects and, in some cases, for operators. These findings are consistent with the current TMS safety guidelines that recommend the use of hearing protection.
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http://dx.doi.org/10.1016/j.brs.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263763PMC
November 2020

Conditions for numerically accurate TMS electric field simulation.

Brain Stimul 2020 Jan - Feb;13(1):157-166. Epub 2019 Oct 3.

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, 27710, USA; Department of Electrical and Computer Engineering, Duke University, Durham, NC, 27708, USA; Department of Neurosurgery, Duke University, Durham, NC, 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA. Electronic address:

Background: Computational simulations of the E-field induced by transcranial magnetic stimulation (TMS) are increasingly used to understand its mechanisms and to inform its administration. However, characterization of the accuracy of the simulation methods and the factors that affect it is lacking.

Objective: To ensure the accuracy of TMS E-field simulations, we systematically quantify their numerical error and provide guidelines for their setup.

Method: We benchmark the accuracy of computational approaches that are commonly used for TMS E-field simulations, including the finite element method (FEM) with and without superconvergent patch recovery (SPR), boundary element method (BEM), finite difference method (FDM), and coil modeling methods.

Results: To achieve cortical E-field error levels below 2%, the commonly used FDM and 1st order FEM require meshes with an average edge length below 0.4 mm, 1st order SPR-FEM requires edge lengths below 0.8 mm, and BEM and 2nd (or higher) order FEM require edge lengths below 2.9 mm. Coil models employing magnetic and current dipoles require at least 200 and 3000 dipoles, respectively. For thick solid-conductor coils and frequencies above 3 kHz, winding eddy currents may have to be modeled.

Conclusion: BEM, FDM, and FEM all converge to the same solution. Compared to the common FDM and 1st order FEM approaches, BEM and 2nd (or higher) order FEM require significantly lower mesh densities to achieve the same error level. In some cases, coil winding eddy-currents must be modeled. Both electric current dipole and magnetic dipole models of the coil current can be accurate with sufficiently fine discretization.
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http://dx.doi.org/10.1016/j.brs.2019.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888902PMC
June 2020

Short-interval intracortical inhibition in human primary motor cortex: A multi-locus transcranial magnetic stimulation study.

Neuroimage 2019 12 13;203:116194. Epub 2019 Sep 13.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Short-interval intracortical inhibition (SICI) has been studied with paired-pulse transcranial magnetic stimulation (TMS) by administering two pulses at a millisecond-scale interstimulus interval (ISI) to a single cortical target. It has, however, been difficult to study the interaction of nearby cortical targets with paired-pulse TMS. To overcome this limitation, we have developed a multi-locus TMS (mTMS) device, which allows controlling the stimulus location electronically. Here, we applied mTMS to study SICI in primary motor cortex with paired pulses targeted to adjacent locations, aiming to quantify the extent of the cortical region producing SICI in the location of a test stimulus. We varied the location and timing of the conditioning stimulus with respect to a test stimulus targeted to the cortical hotspot of the abductor pollicis brevis (APB) in order to study their effects on motor evoked potentials. We further applied a two-coil protocol with the conditioning stimulus given by an oval coil only to the surroundings of the APB hotspot, to which a subsequent test stimulus was administered with a figure-of-eight coil. The strongest SICI occurred at ISIs below 1 ms and at ISIs around 2.5 ms. These ISIs increased when the conditioning stimulus receded from the APB hotspot. Our two-coil paired-pulse TMS study suggests that SICI at ISIs of 0.5 and 2.5 ms originate from different mechanisms or neuronal elements.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116194DOI Listing
December 2019

Real-time computation of the TMS-induced electric field in a realistic head model.

Neuroimage 2019 12 5;203:116159. Epub 2019 Sep 5.

Aalto University, Department of Neuroscience and Biomedical Engineering, P.O. Box 12200, FI-00076, Aalto, Finland.

Transcranial magnetic stimulation (TMS) is often targeted using a model of TMS-induced electric field (E). In such navigated TMS, the E-field models have been based on spherical approximation of the head. Such models omit the effects of cerebrospinal fluid (CSF) and gyral folding, leading to potentially large errors in the computed E-field. So far, realistic models have been too slow for interactive TMS navigation. We present computational methods that enable real-time solving of the E-field in a realistic five-compartment (5-C) head model that contains isotropic white matter, gray matter, CSF, skull and scalp. Using reciprocity and Geselowitz integral equation, we separate the computations to coil-dependent and -independent parts. For the Geselowitz integrals, we present a fast numerical quadrature. Further, we present a moment-matching approach for optimizing dipole-based coil models. We verified and benchmarked the new methods using simulations with over 100 coil locations. The new quadrature introduced a relative error (RE) of 0.3-0.6%. For a coil model with 42 dipoles, the total RE of the quadrature and coil model was 0.44-0.72%. Taking also other model errors into account, the contribution of the new approximations to the RE was 0.1%. For comparison, the RE due to omitting the separation of white and gray matter was >11%, and the RE due to omitting also the CSF was >23%. After the coil-independent part of the model has been built, E-fields can be computed very quickly: Using a standard PC and basic GPU, our solver computed the full E-field in a 5-C model in 9000 points on the cortex in 27 coil positions per second (cps). When the separation of white and gray matter was omitted, the speed was 43-65 cps. Solving only one component of the E-field tripled the speed. The presented methods enable real-time solving of the TMS-induced E-field in a realistic head model that contains the CSF and gyral folding. The new methodology allows more accurate targeting and precise adjustment of stimulation intensity during experimental or clinical TMS mapping.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116159DOI Listing
December 2019

The effect of experimental pain on short-interval intracortical inhibition with multi-locus transcranial magnetic stimulation.

Exp Brain Res 2019 Jun 27;237(6):1503-1510. Epub 2019 Mar 27.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, AALTO, P.O. Box 12200, 00076, Espoo, Finland.

Chronic neuropathic pain is known to alter the primary motor cortex (M1) function. Less is known about the normal, physiological effects of experimental neurogenic pain on M1. The objective of this study is to determine how short-interval intracortical inhibition (SICI) is altered in the M1 representation area of a muscle exposed to experimental pain compared to SICI of another muscle not exposed to pain. The cortical representation areas of the right abductor pollicis brevis (APB) and biceps brachii (BB) muscles of 11 subjects were stimulated with a multi-locus transcranial magnetic stimulation device while the resulting motor-evoked potentials (MEPs) were recorded with electromyography. Single- and paired-pulse TMS was administered in seven conditions, including one with the right hand placed in cold water. The stimulation intensity for the conditioning pulses in the paired-pulse examination was 80% of the resting motor threshold (RMT) of the stimulated site and 120% of RMT for both the test and single pulses. The paired-pulse MEP amplitudes were normalized with the mean amplitude of the single-pulse MEPs of the same condition and muscle. SICI was compared between conditions. After the cold pain, the normalized paired-pulse MEP amplitudes decreased in APB, but not in BB, indicating that SICI was potentially increased only in the cortical area of the muscle subjected to pain. These data suggest that SICI is increased in the M1 representation area of a hand muscle shortly after exposure to pain has ended, which implies that short-lasting pain can alter the inhibitory balance in M1.
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http://dx.doi.org/10.1007/s00221-019-05502-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525662PMC
June 2019

Multi-locus transcranial magnetic stimulation-theory and implementation.

Brain Stimul 2018 Jul - Aug;11(4):849-855. Epub 2018 Mar 23.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation.

Objective: To overcome the limitations of physical TMS-coil movement by introducing electronic targeting.

Methods: We propose electronic stimulation targeting using a set of large overlapping coils and introduce a matrix-factorisation-based method to design such sets of coils. We built one such device and demonstrated the electronic stimulation targeting in vivo.

Results: The demonstrated two-coil transducer allows translating the stimulated spot along a 30-mm-long line segment in the cortex; with five coils, a target can be selected from within a region of the cortex and stimulated in any direction. Thus, far fewer coils are required by our approach than by previously suggested ones, none of which have resulted in practical devices.

Conclusion: Already with two coils, we can adjust the location of the induced electric field maximum along one dimension, which is sufficient to study, for example, the primary motor cortex.
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http://dx.doi.org/10.1016/j.brs.2018.03.014DOI Listing
February 2019

Noninvasive extraction of microsecond-scale dynamics from human motor cortex.

Hum Brain Mapp 2018 06 2;39(6):2405-2411. Epub 2018 Mar 2.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland.

State-of-the-art noninvasive electromagnetic recording techniques allow observing neuronal dynamics down to the millisecond scale. Direct measurement of faster events has been limited to in vitro or invasive recordings. To overcome this limitation, we introduce a new paradigm for transcranial magnetic stimulation. We adjusted the stimulation waveform on the microsecond scale, by varying the duration between the positive and negative phase of the induced electric field, and studied corresponding changes in the elicited motor responses. The magnitude of the electric field needed for given motor-evoked potential amplitude decreased exponentially as a function of this duration with a time constant of 17 µs. Our indirect noninvasive measurement paradigm allows studying neuronal kinetics on the microsecond scale in vivo.
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http://dx.doi.org/10.1002/hbm.24010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866442PMC
June 2018

Coil optimisation for transcranial magnetic stimulation in realistic head geometry.

Brain Stimul 2017 Jul - Aug;10(4):795-805. Epub 2017 Apr 15.

Department of Neuroscience and Biomedical Engineering, Aalto University, P.O. Box 12200, FI-00076 AALTO, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, P.O. Box 340, FI-00029 HUS, Helsinki, Finland.

Background: Transcranial magnetic stimulation (TMS) allows focal, non-invasive stimulation of the cortex. A TMS pulse is inherently weakly coupled to the cortex; thus, magnetic stimulation requires both high current and high voltage to reach sufficient intensity. These requirements limit, for example, the maximum repetition rate and the maximum number of consecutive pulses with the same coil due to the rise of its temperature.

Objective: To develop methods to optimise, design, and manufacture energy-efficient TMS coils in realistic head geometry with an arbitrary overall coil shape.

Methods: We derive a semi-analytical integration scheme for computing the magnetic field energy of an arbitrary surface current distribution, compute the electric field induced by this distribution with a boundary element method, and optimise a TMS coil for focal stimulation. Additionally, we introduce a method for manufacturing such a coil by using Litz wire and a coil former machined from polyvinyl chloride.

Results: We designed, manufactured, and validated an optimised TMS coil and applied it to brain stimulation. Our simulations indicate that this coil requires less than half the power of a commercial figure-of-eight coil, with a 41% reduction due to the optimised winding geometry and a partial contribution due to our thinner coil former and reduced conductor height. With the optimised coil, the resting motor threshold of abductor pollicis brevis was reached with the capacitor voltage below 600 V and peak current below 3000 A.

Conclusion: The described method allows designing practical TMS coils that have considerably higher efficiency than conventional figure-of-eight coils.
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http://dx.doi.org/10.1016/j.brs.2017.04.001DOI Listing
February 2018

Experimental Characterization of the Electric Field Distribution Induced by TMS Devices.

Brain Stimul 2015 May-Jun;8(3):582-9. Epub 2015 Jan 12.

Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Espoo, Finland; BioMag Laboratory, HUS Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Aalto TMS Laboratory, Aalto Neuroimaging, Aalto University, Espoo, Finland.

Background: In transcranial magnetic stimulation (TMS) a strong, brief current pulse driven through a coil is used for non-invasively stimulating the cortex. Properties of the electric field (E-field) induced by the pulse together with physiological parameters determine the outcome of the stimulation. In research and clinical use, TMS is delivered using a wide range of different coils and stimulator units, all having their own characteristics; however, the parameters of the induced E-field are often inadequately known by the user.

Objective: To better understand how the use of a specific TMS device may affect the resulting cortical stimulation, our objective was to develop an instrument for automated measurement of the E-fields induced by TMS coils in spherically symmetric conductors approximating the head.

Methods: We built a saline-free, robotized measurement tool based on the triangle construction. The 5-mm-wide measurement probe allows complete sampling of the induced E-field at the studied depth. We used the instrument to characterize TMS coils and stimulators made by two companies.

Results: The measurements revealed that all tested stimulators performed as expected, but we also found significant differences between the different stimulators. Measurements of different coil specimens of the same stimulator models agreed with each other.

Conclusion: The presented TMS calibrator allows a straightforward characterization of the E-fields induced by TMS coils. By performing measurements using this kind of a tool helps in ensuring that an investigator knows the properties of the E-field.
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http://dx.doi.org/10.1016/j.brs.2015.01.004DOI Listing
January 2016

Minimum-energy coils for transcranial magnetic stimulation: application to focal stimulation.

Brain Stimul 2015 Jan-Feb;8(1):124-34. Epub 2014 Oct 13.

Department of Biomedical Engineering and Computational Science (BECS), Aalto University, P.O. Box 12200, FI-00076 AALTO, Espoo, Finland.

Background: In transcranial magnetic stimulation (TMS), the stimulation-coil current is typically increased from 0 to over 5000 A in less than 100 μs. At the peak current, the energy stored in the magnetic field is over 300 J. Thus, the average power during a pulse exceeds 3 MW; the stimulator needs to be built from high-power electronics. The power requirements often limit the duration and frequency of repetitive TMS, for example, via coil heating.

Objective: We introduce a method for finding the minimum-energy solution for a TMS coil with given focality constraints.

Methods: This optimization is performed by using a spherically symmetric head model and by expressing the coil as a continuous surface current density, which is eventually discretized to form the coil windings. For the optimization, we defined TMS focality separately for the directions parallel and perpendicular to the field direction at the maximum of induced electric field.

Results: The computational model used for optimization was verified by manufacturing a prototype coil and measuring the electric field it induces in a spherically symmetric conductor. The optimized coil design requires significantly less power than existing TMS coil designs (a 73% reduction compared to an existing TMS coil with similar focality).

Conclusion: The described method allows for more efficient, more focal TMS coils, which may reduce coil heating and the coil click.
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http://dx.doi.org/10.1016/j.brs.2014.10.002DOI Listing
May 2015
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